Hydrochloric Acid → HCID 66712317, compound

HRID 1262433Notes

Reaction equation

HRID 1262433 reaction equation
Br[C:2]1[N:10]2[C:5]([CH:6]=[N:7][C:8]([S:11][CH3:12])=[N:9]2)=[CH:4][CH:3]=1.[NH2:13][C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][C:15]=1B(O)O.C(=O)([O-])[O-].[Na+].[Na+].O.Cl>C(O)C.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.O1CCCC1>[CH3:12][S:11][C:8]1[N:7]=[CH:6][C:5]2=[CH:4][CH:3]=[C:2]([C:15]3[CH:16]=[CH:17][CH:18]=[CH:19][C:14]=3[NH2:13])[N:10]2[N:9]=1

Participants

9

Reactant 5

HCID 313Hydrochloric AcidHCID 962WaterHCID 10340Sodium CarbonateHCID 2773216(2-Aminophenyl)boronic acidHCID 574161287-Bromo-2-(methylsulfanyl)pyrrolo[2,1-f][1,2,4]triazine

Product 1

HCID 66712317HCID 66712317, compoundYield 74.2%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 702EthanolSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
75 °C

Procedure

7-Bromo-2-methylsulfanyl-pyrrolo[2,1-f][1,2,4]triazine (1.00 g, 4.10 mmol), 2-aminophenylboronic acid pinocl ester (1.84 g, 8.40 mmol), and Tetrakis(triphenylphosphine)palladium(0) (0.710 g, 0.614 mmol) were dissolved in Ethanol (15 mL) and Tetrahydrofuran (15 mL) followed by addition of 2.00 M of Sodium carbonate in Water (5.0 mL, 10 mmol). The reaction mixture was then heated at 75° C. and was allowed to stir overnight. After cooling to room temperature, the reaction mixture was acidified with ˜2 mL concentrated HCl and then extracted with EtOAc (2×, 30 mL). The organics were then back extracted with 3M HCl (2×, 20 mL) and the aqueous layers combined and washed with EtOAc (2×, 20 mL). The combined HCl was then basified while stirring with 5N NaOH followed by extraction with DCM (3×, 30 mL) and brine, drying with sodium sulfate, and conc. in vacuo. The product was then purified by ISCO column chromatography (50/50 EtOAc/Hex, 40 g column) to afford 2-(2-Methylsulfanyl-pyrrolo[2,1-f][1,2,4]triazin-7-yl)-phenylamine as a white solid (0.78 g, 74%). LCMS: 257 (M+H). 1H-NMR (CDCl3): 8.74 (s, 1H), 7.44 (d, 1H, J=7.72 Hz), 6.98 (d, 1H, J=4.82 Hz), 6.94 (d, 1H, J=4.82 Hz), 6.88 (d, 1H, J=7.78 Hz), 6.84 (d, 1H, J=7.78 Hz), 4.12 (m, 2H), 2.50 (s, 3H).

Workup

  1. temperatureAfter cooling to room temperature
  2. extractionextracted with EtOAc (2×, 30 mL)
  3. extractionThe organics were then back extracted with 3M HCl (2×, 20 mL)
  4. washwashed with EtOAc (2×, 20 mL)
  5. stirringwhile stirring with 5N NaOH
  6. extractionfollowed by extraction with DCM (3×, 30 mL) and brine
  7. dry with materialdrying with sodium sulfate
  8. customThe product was then purified by ISCO column chromatography (50/50 EtOAc/Hex, 40 g column)

Sources & evidence

ORD record
ord-96f7640d008a4a6894aafbee68e12bd3
Source dataset
uspto-grants-2013_06
Patent number
US08471005B2

Reaction notes

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